Galthie also announced that Dorian Aldegheri will replace Uini Atonio as tighthead prop.
Scrumhalf Dupont, who suffered a ruptured anterior cruciate ligament in March 2025 against Ireland, missed the end of last year’s autumn programme before he resumed playing for Toulouse in November.
"Antoine Dupont is an asset in many areas, but he also demands more, pushing us to raise our work level to match the ambition he carries within him," Galthie told a press conference on Tuesday.
The 2020, 2022, and 2023 player of the tournament will be paired with Matthieu Jalibert, who has not played for Les Bleus for a year. The flyhalf benefits from Romain Ntamack's injury and has also enjoyed strong performances with Bordeaux.
During the last Six Nations edition, Jalibert was only included against England during the second matchday when Ntamack was suspended.
Aldegheri was picked as tighthead prop ahead of Regis Montagne, following Atonio's career-ending cardiac incident last week.
Aldegheri last started with the France team during the 2023 World Cup pool stage.
"Dorian (Aldegheri) is starting because he now demonstrates mastery of the position and experience," Galthie said.
The France coach has also handed a start to winger Theo Attissogbe, filling the position left vacant by Damian Penaud, France's all-time leading try scorer, who had not been included in the preliminary squad ahead of the tournament.
"He started his journey with us in Argentina (in 2024). I said that there are some gems in this team, and Theo (Attissogbe) is one of them," Galthie added.
France are hosting Ireland on Thursday so that the fixture avoids clashing with Friday's opening ceremony of the Winter Olympics.
France team:
15-Thomas Ramos, 14-Theo Attissogbe, 13-Nicolas Depoortere, 12-Yoram Moefana, 11-Louis Bielle-Biarrey, 10-Matthieu Jalibert, 9-Antoine Dupont (captain), 8-Anthony Jelonch, 7-Francois Cros, 6-Oscar Jegou, 5-Mickael Guillard, 4-Charles Ollivon, 3-Dorian Aldegheri, 2-Julien Marchand, 1-Jean-Baptiste Gros
Replacements: 16-Peato Mauvaka, 17-Rodrigue Neti, 18-Regis Montagne, 19-Hugo Auradou, 20-Emmanuel Meafou, 21-Lenni Nouchi, 22-Baptiste Serin, 23-Kalvin Gourgues.
